Vioxx, Bextra and Meridia are all drugs that increase blood pressure which were only determined to increase the risk of heart attack and stroke subsequent to approval. Other drugs that can raise blood pressure, including pharmaceuticals that address attention deficit disorder and depression, continue to remain on the market. “It is unwise to allow medications that predictably increase risk to be marketed without adequate safety data,” stated Dr Blankfield, who is a family physician at University Hospitals Berea Health Center. “Risk should be quantified, and the product label should accurately communicate the risk.”

The authors of the editorial suggest that the FDA establish guidelines concerning the amount of blood pressure increase that constitutes a risk for varying populations and to require pharmaceutical companies to provide cardiovascular safety data on drugs that elevate blood pressure and to post data or warnings on drug labels. “This would allow physicians and patients to make informed decisions about medications,” he stated. “Physicians and the general public may assume that if a drug is approved by the FDA, it is safe. Yet even modest elevations in blood pressure increase the risk of heart attacks and strokes.”

Melatonin supplementation improves bone quality in aged rodents

May 28 2014. In an article published online on March 11, 2014 in the journal Rejuvenation Research, scientists at the University of Madrid report a bone benefit for melatonin in elderly rats.

“Previous studies have shown that melatonin, an antioxidant molecule secreted from the pineal gland, is a positive regulator of bone mass,” write Faleh Tamini and colleagues in their introduction. “However, melatonin’s potential effects on bone mass have never been investigated in old population yet.”

The study utilized 22 month old male Wistar rats. (Twenty-two months of age in rats is the approximate equivalent of 60 years of age in humans.) Ten animals given melatonin-enhanced drinking water for ten weeks were compared to an equal number that received unenhanced water. At the end of the treatment period, the rats’ femurs (leg bones) were tested for density and strength.

Bone from animals that received melatonin had greater volume, strength and density, which suggests that melatonin could be of value in the prevention of human osteoporosis. “These compelling results are the first evidence indicating that dietary melatonin supplementation is able to exert beneficial effects against age-related bone loss in old rats; improving the microstructure and biomechanical properties of aged bones,” the authors announce.

"As we age, we sleep less well, which means that the osteoclasts are more active," commented lead researcher Tamimi, who is a professor in the School of Dentistry at McGill University in Montreal. “This tends to speed up the process of bone breakdown."

Dr Tamimi’s team plans to determine whether melatonin protects against osteoporosis or actually reverses it. "I am applying for funding to pursue the research and we hope to have answers soon," he said.

Adding metformin to antiaging drug improves safety

May 26 2014. An article published online on April 22, 2014 in the Journals of Gerontology®: Biological Sciences provides more information on the action of rapamycin, an immunosuppressant drug that is also a calorie restriction mimetic. Calorie restriction is currently the gold standard therapy to delay the effects of aging, yet the technique is often challenging to practice, leading to a search for a nutrient or drug that can provide similar benefits.

While rapamycin has been shown to increase both health span and life span in mice, the compound can induce insulin resistance, which makes it a less attractive candidate for treating human aging. The current research compared aspects of liver metabolism in mice treated with rapamycin or calorie restriction for six months. They found that both techniques inhibited the synthesis of lipids, but only calorie restriction increased their oxidation in the production of energy, while rapamycin permitted a buildup of fatty acids, which can lead to insulin resistance.

Authors Viviana I. Pérez and her associates report that the repressed fatty acid oxidation induced by rapamycin was rescued in vitro by the administration of the diabetes drug metformin, which affects insulin and IGF1 signaling. “If proven true, then combined use of metformin and rapamycin for treating aging and age-associated diseases in humans may be possible,” they conclude.

“This could be an important advance if it helps us find a way to gain the apparent benefits of rapamycin without increasing insulin resistance,” stated Dr Perez, who is an assistant professor in the Department of Biochemistry and Biophysics in the Oregon State University College of Science. “It could provide a way not only to increase lifespan but to address some age-related diseases and improve general health. We might find a way for people not only to live longer, but to live better and with a higher quality of life.”

Supplementation with magnesium lowers CRP in prediabetics

May 23 2014. An article published online on May 7, 2014 in the Archives of Medical Research reports the results of a double-blinded trial of subjects with prediabetes and low magnesium levels which found a benefit for magnesium supplementation in reducing C-reactive protein (CRP), a marker of inflammation.

The trial included 62 men and women between the ages of 18 to 65 years with newly diagnosed prediabetes who had magnesium levels below 0.74 micromoles per liter (mmol/L). Participants received an oral magnesium chloride solution containing 382 milligrams magnesium or a placebo daily for three months, and both groups received advice concerning physical activity and the components of a healthy diet. Plasma glucose, serum magnesium and high-sensitivity C-reactive protein (hsCRP) were measured before and after the treatment period.

By the end of the study, serum magnesium levels were higher, and fasting and two hour post-load glucose levels were lower among those who received magnesium in comparison with the placebo. While both groups experienced a decline in CRP, the decrease was significantly greater among those who received magnesium.

Authors Luis E. Simental-Mendía and colleagues note that magnesium deficiency has been proposed as an early factor in the activation of the inflammatory response. They recommend further clinical trials to establish whether magnesium deficiency plays a causative role in inflammation and to determine its mechanisms.

"Our results show that oral magnesium supplementation significantly decreases hsCRP levels in apparently healthy subjects with prediabetes and hypomagnesemia," the authors write. "Taking into account that elevated hsCRP is related to glucose metabolic disorders, our finding may have important implications in the policies focused in its prevention."

Researchers at the Riddet Institute and the University of Ontago in New Zealand selected forty trials for their analysis, which included a total of 1,699 men and women. Thirty-nine of the studies provided data concerning lipid levels and twelve reported blood pressure. Studies included those in which dietary interventions intended to alter sugar intake in one group of participants were compared to a group with a differing intake. The researchers found an association between increased sugar intake and higher total cholesterol and triglycerides in comparison with levels measured in subjects who had a lower intake, which was particularly strong in subgroup analyses of studies in which no significant difference in weight change occurred between the groups. An association between greater sugar intake and higher systolic blood pressure was observed in trials lasting eight weeks or more.

May 19 2014. An article published on April 29, 2014 in the British Medical Journal reveals an increase in the number of years lived by myocardial infarction (MI, or heart attack) survivors who consume a greater amount of fiber.

Doctoral candidate Shanshan Li of Harvard School of Public Health and colleagues utilized data from 1,840 men enrolled in the Health Professional Follow-Up Study and 2,258 women from the Nurses’ Health Study who had survived an initial heart attack during the studies’ follow-up periods. Dietary questionnaires completed every four years provided information on fiber intake before and after the heart attack. In a pooled analysis of all subjects, those whose post-MI intake of fiber was among the top one-fifth of participants had a 25% lower risk of dying from any cause over a nine year average follow-up in comparison with those whose intake was among the lowest fifth. When fiber was analyzed by source, cereal fiber emerged as significantly protective.

Heart attack survivors who increased their fiber intake from levels consumed before the event also experienced a decrease in all-cause as well as cardiovascular mortality. Among those whose intake of fiber was among the highest one-third prior to and following their events, there was a 27% lower risk of death in comparison with those whose intake was among the lowest third in both phases.

As possible mechanisms supporting the current findings, the authors list reductions in inflammation, low density lipoprotein (LDL) cholesterol and lipid peroxidation, as well as improvements in insulin sensitivity, glycemic control and gut microbiota.

“Future research on lifestyle changes post-MI should focus on a combination of lifestyle changes and how they may further reduce mortality rates beyond what is achievable by medical management alone,” they conclude.

Zinc supplementation aids in the prevention of premature mortality in children suffering from malnutrition

May 16 2014. The Cochrane Library published a review on May 15, 2014 which concluded that supplementing with zinc reduced the risk of morbidity and mortality, and improved growth in malnourished children.

Professor Zulﬁqar Bhutta of the Center of Excellence in Women and Child Health at Aga Khan University in Karachi, Pakistan and colleagues selected 80 randomized controlled trials that included a total of 205,401 boys and girls between the ages of 6 months and 12 years for their review. They found that supplementing with zinc decreased the risk of diarrhea, a major cause of death among children in developing countries. Zinc supplementation was also associated with a reduction in the risk of mortality from diarrhea, lower respiratory tract infection and malaria, as well as death from all causes. Additionally, children who supplemented with zinc were slightly taller at the end of the trials included in the current study, in comparison with those who did not supplement.

"We should remember that supplements are not a substitute for a well-balanced diet," noted Dr Bhutta, who is also affiliated with the Sick Kids Center for Global Child Health in Toronto. "However, in countries where zinc deficiency is common, supplements may help to reduce child deaths and related diseases in the short-term."

The study is the first Cochrane review of zinc in the prevention of childhood mortality. "Policymakers in low and middle income countries need evidence that directly addresses the needs of their own health services,” noted Dr David Tovey, who is the Cochrane Library’s Editor-in-Chief. “This comprehensive review makes a very valuable contribution to the evidence base around interventions may make an important contribution to improving global health."

The purpose-driven life

May 14 2014. An article published online on May 8, 2014 in Psychological Science links having a purpose in life to a reduced risk of premature mortality.

“Having a purpose in life has been cited consistently as an indicator of healthy aging for several reasons, including its potential for reducing mortality risk,” write authors Patrick L. Hill and Nicholas A. Turiano. “In the current study, we sought to extend previous findings by examining whether purpose in life promotes longevity across the adult years.”

By evaluating data from over 6,000 men and women enrolled in the Midlife in the United States study, Hill and Turiano uncovered an association between a greater sense of purpose and a reduced risk of dying over fourteen years of follow-up. The survival benefit was not related to age or retirement status.

“There are a lot of reasons to believe that being purposeful might help protect older adults more so than younger ones,” stated Dr Hill, who is affiliated with Carleton University’s Department of Psychology. “For instance, adults might need a sense of direction more, after they have left the workplace and lost that source for organizing their daily events. In addition, older adults are more likely to face mortality risks than younger adults.”

The authors are currently attempting to determine if the reason for the study’s finding is due to the practice of healthier lifestyles among those having a purpose. They also plan to explore the effect of purpose on other aspects of well-being.

“Our findings point to the fact that finding a direction for life, and setting overarching goals for what you want to achieve can help you actually live longer, regardless of when you find your purpose,” Dr Hill noted. “So the earlier someone comes to a direction for life, the earlier these protective effects may be able to occur.”

Deficient vitamin D levels predict prostate cancer aggressiveness

May 5 2014. The May 1, 2014 issue of the journal Clinical Cancer Research published the finding of Northwestern University researchers of an association between vitamin D deficiency and a greater risk of prostate cancer as well as more aggressive disease.

Among African-Americans, having a deficient vitamin D level of less than 20 nanograms per milliliter (ng/mL) was associated with more than double the risk of having a biopsy result that was diagnostic of prostate cancer in comparison with men who had higher levels of the vitamin. A severely deficient vitamin D level of less than 12 ng/mL was associated with significantly greater odds of increased tumor aggressiveness and tumor stage in both African and European-Americans.

"Vitamin D deficiency could be a biomarker of advanced prostate tumor progression in large segments of the general population," commented Dr Murphy, who is an assistant professor in urology at Northwestern University Feinberg School of Medicine. "More research is needed, but it would be wise for men to be screened for vitamin D deficiency and treated."

"Vitamin D deficiency is more common and severe in people with darker skin and it could be that this deficiency is a contributor to prostate cancer progression among African-Americans," he noted. "Our findings imply that vitamin D deficiency is a bigger contributor to African-American prostate cancer."

"It is a good idea to get your levels checked on a yearly basis," Dr Murphy recommended. "If you are deficient, you and your doctor can make a plan on how to reverse it through diet, supplements or other therapies."

Compound extends life in mouse model of accelerated aging

May 2 2014. An article published online on April 28, 2014 in the Proceedings of the National Academy of Sciences reports the outcome of a quarter of a decade of research conducted by Douglas E. Vaughan, MD, and his colleagues at Northwestern University, which identified a drug that could one day prolong human life.

Acting on the knowledge of an age-related reduction in the ability of cells to secrete specific proteins, including one known as plasminogen activator inhibitor (PAI-1) related to cardiovascular disease, Dr Vaughn explained that his team “made the intellectual leap between a marker of senescence and physiological aging. We asked is this marker for cell aging one of the drivers or mechanisms of rapid physiological aging?"

To find out, they added an experimental compound labeled TM5441 to the diet of mice deficient in the aging-suppressive gene Klotho. Mice lacking Klotho rapidly develop osteoporosis, neurodegeneration and other conditions, and die at a younger age than normal mice.

In addition to decreasing the activity of PAI-1, the Klotho-deficient animals lived four times longer than usual while maintaining healthy organ function. When these mice were bred with PAI-1 deficient mice, similar benefits were observed. "A drug like this could help reduce complications in clinical conditions that reflect accelerated aging," commented Dr Vaughan, who is the chair of Medicine at Northwestern University’s Feinberg School of Medicine and physician in chief at Northwestern Memorial Hospital. "This had a very robust effect in terms of prolonging life span."

Although TM5441 is only in its early stages of testing, Dr Vaughn stated that “It makes sense that this might be one component of a cocktail of drugs or supplements that a person might take in the future to extend their healthy life.”

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